Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain.

@article{Murthy2007IrreversibleBO,
  title={Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain.},
  author={V. Murthy and Huw M. L. Davies and Simon J. Hedley and Steven R. Childers},
  journal={Biochemical pharmacology},
  year={2007},
  volume={74 2},
  pages={
          336-44
        }
}
Irreversible tropane analogs have been useful in identifying binding sites of cocaine on biogenic amine transporters, including transporters for dopamine (DAT), serotonin (SERT) and norepinephrine (NET). The present study characterizes the properties of the novel phenylisothiocyanate tropane HD-205, synthesized from the highly potent 2-napthyl tropane analog WF-23. In radioligand binding studies in brain membranes, direct IC(50) values of HD-205 were 4.1, 14 and 280nM at DAT, SERT and NET… Expand
In Vivo Characterization of a Novel Phenylisothiocyanate Tropane Analog at Monoamine Transporters in Rat Brain
TLDR
The irreversible effects of HD-205 in vivo in rats after intracranial injection was evaluated to evaluate the neuroanatomical basis of DAT-mediated cocaine effects and a strategy of site-specific chemical blockade of transporters was proposed. Expand
A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone.
TLDR
A ligand was synthesized in which the aromatic ring of pyrovalerone was substituted with a photoreactive azido group, demonstrating appreciable binding affinity for the dopamine transporter and suggesting the potential utility of a radioiodinated version in structure-function studies of this protein. Expand
Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling.
TLDR
Compound (±)-3a represents the first successful example of a DAT photoaffinity ligand based on the methylphenidate scaffold and is expected to assist in mapping non-tropane ligand-binding pockets within plasma membrane monoamine transporters. Expand

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